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Low Molecular Pectin Inhibited the Lipid Accumulation by Upregulation of METTL7B
Xiaojin Yang1, Yinghua Yuan2, Desheng Xie1
1Department of Infectious Diseases, Shanghai Fifth People's Hospital, Fudan University, No. 128 Ruili Road, Shanghai, 200240, China.
Abstract:
Inhibition of lipid accumulation is the key step to prevent nonalcoholic fatty liver (NAFL) progressing to nonalcoholic steatohepatitis. We aimed to study the effect of low-molecular-weight citrus pectin (LCP) against lipid accumulation and the underlying mechanism. Oleic acid (OA)-induced lipid deposition in HepG2 cells was applied to mimic in vitro model of lipid accumulation. Oil Red O (ORO) stain result showed lipid accumulation was significantly reduced, and levels of adipose triglyceride lipase (ATGL) and carnitine palmitoyltransferase-1 (CPT-1), involved in triacylglycerol catabolism and fatty acid β-oxidation, detected by RT-qPCR were increased after OA-stimulated HepG2 cells treated with LCP. RNA sequencing analysis identified 740 differentially expressed genes (DEGs) in OA-stimulated HepG2 cells treated with the LCP group (OA+LCP group), and bioinformatics analysis indicated that some DEGs were enriched in lipid metabolism-related processes and pathways. The expression of the top 8 known DEGs in the OA+LCP group was then verified by RT-qPCR, which showed that fold change (abs) of METTL7B was the highest among the 8 candidates. In addition, overexpression of METTL7B in HepG2 cells significantly inhibited the lipid accumulation and enhanced levels of ATGL and CPT-1. In conclusion, LCP inhibited lipid accumulation through the upregulation of METTL7B, and further enhancement of ATGL and CPT-1 levels. LCP is expected to develop as a promising agent to ameliorate fat accumulation in NAFL.
Insights
Low-molecular-weight citrus pectin (LCP) reduces liver fat accumulation by increasing METTL7B, adipose triglyceride lipase (ATGL), and carnitine palmitoyltransferase-1 (CPT-1) levels. This suggests LCP may prevent nonalcoholic fatty liver disease progression.
Area of Science:
- Biochemistry
- Cell Biology
- Nutritional Science
Background:
- Nonalcoholic fatty liver (NAFL) progression to nonalcoholic steatohepatitis is linked to lipid accumulation.
- Targeting lipid accumulation is crucial for preventing NAFL progression.
Purpose of the Study:
- To investigate the effect of low-molecular-weight citrus pectin (LCP) on lipid accumulation in liver cells.
- To elucidate the underlying molecular mechanisms of LCP's action.
Main Methods:
- An in vitro model using oleic acid (OA)-induced lipid deposition in HepG2 cells.
- Oil Red O staining to quantify lipid accumulation.
- RT-qPCR and RNA sequencing to analyze gene expression, including ATGL, CPT-1, and METTL7B.
Main Results:
- LCP significantly reduced OA-induced lipid accumulation in HepG2 cells.
- LCP treatment increased the expression of ATGL and CPT-1, key enzymes in lipid metabolism.
- RNA sequencing identified METTL7B as a significantly upregulated gene, which, upon overexpression, also inhibited lipid accumulation and enhanced ATGL and CPT-1 levels.
Conclusions:
- LCP inhibits lipid accumulation in liver cells, potentially by upregulating METTL7B.
- The mechanism involves enhancing enzymes involved in triacylglycerol catabolism and fatty acid oxidation.
- LCP shows promise as a therapeutic agent for managing fat accumulation in NAFL.
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